APPLICANT'S DESCRIPTION: Cognitive deficits associated with cancer treatment can have a dramatic effect on patients' quality of life and have been recognized as a problem by the President's Cancer Panel (1999) and the National Coalition for Cancer Survivorship as a challenge facing people with cancer. The present application is an extension of work completed by researchers at Dartmouth with a supplement from the Office of Cancer Survivors to the Norris Cotton Cancer Center Core grant (Grant No. P30CA23 108, supplement) entitled "Cognitive Impact of Systemic Chemotherapy in Long-Term Survivors of Breast Cancer and Lymphoma." Survivors who were greater than 5 years post-diagnosis and disease free were administered a battery of standardized neuropsychological and psychological tests. The results demonstrated that survivors who had been treated with systemic chemotherapy scored significantly lower in overall neuropsychological functioning as compared to survivors who had been treated with local therapy only. In this next phase of research, we propose to prospectively study the cognitive deficits experienced by breast cancer and lymphoma patients treated with their first course of systemic chemotherapy versus local surgery or non-CNS radiation. Patients will be assessed at pre-treatment and 6, 12 and 24 months post-diagnosis with a standardized battery of neuropsychological and psychological tests. The primary hypothesis is that patients treated with systemic chemotherapy will demonstrate greater decrements in performance from pre- to post-treatment on standardized measures of neuropsychological functioning as compared to patients treated with local therapy only after controlling for important confounding variables such as age, education, and psychological state. Secondarily, we will evaluate the associations between cognitive functioning and other factors that may effect cognition in cancer patients including genetic markers (APOE status), metabolic factors, menopausal status (pre- vs. post-menopausal at diagnosis), and use of tamoxifen (breast cancer only).